tbuckley/cabot-search huggingface dataset:
Phase 1 first-in-human dose-escalation study of ANV419 in patients with relapsed/refractory advanced solid tumors
Authors: Markus Joerger, Emiliano Calvo, Heinz Laubli, Juanita Lopez, Guzmán Alonso, Elena Corral de la Fuente, Dagmar Hess, David König, Vicky Sanchez Perez, Christoph Bucher, Sangeeta Jethwa, Elena Garralda
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background ANV419 is a stable antibody–cytokine fusion protein consisting of interleukin-2 (IL-2) fused to an anti-IL-2 monoclonal antibody that sterically hinders binding of IL-2 to the α subunit of its receptor but has selective affinity for the receptor βγ subunits. Thus, ANV419 preferentially stimulates CD8 + effector T cells and natural killer cells which are associated with tumor killing, while minimizing the activation of immunosuppressive regulatory T cells. Methods ANV419-001 is an open-label, multicenter, phase 1 study to evaluate the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ANV419. Secondary objectives were to characterize the pharmacokinetics, pharmacodynamics and tumor response. Adult patients with advanced solid tumors and disease progression after ≥1 previous line of systemic therapy were enrolled. ANV419 was administered by intravenous infusion once every 2 weeks, with a planned treatment duration of 12 months. The dose escalation part of the study explored doses 3, 6 and 12 µg/kg as single patient cohorts followed by 24–364 µg/kg in a 3+3 design. Interim results are reported here (data cut-off: March 22, 2023). Results Forty patients were enrolled and received at least one dose of ANV419. The MTD and RP2D were determined to be 243 µg/kg. The most common ANV419-related treatment-emergent adverse events were Grade 1 and 2 fever (31 (77.5%)), chills (23 (57.5%), vomiting (14 (35.0%)), cytokine release syndrome and nausea (12 (30.0%) each). Transient and self-limiting lymphopenia due to lymphocyte redistribution was observed in all patients. In the RP2D cohort, Grade ≥3 thrombocytopenia and fever were reported by one patient (12.5%) each. All events were manageable with standard supportive care. At doses of 243 µg/kg (RP2D/MTD), the estimated T 1/2 was approximately 12 hours. At ANV419 doses ≥108 µg/kg, 64% of patients had a best response of at least SD (15 SD and 1 confirmed PR). Conclusions ANV419 at doses up to 243 µg/kg (the RP2D) was well tolerated and showed signs of antitumor activity in a heavily pretreated patient population with advanced solid tumors. Trial registration number NCT04855929 .
Novel treatments for novel side effects: a case report and review of baricitinib use in the treatment of chronic inflammatory demyelinating polyneuropathy caused by immune checkpoint inhibitor use
Authors: Sana Haider, Wei Chua, Bavanthi Balakrishnar, Stephen Della-Fiorentina, Tara Laurine Roberts, Karuna Keat
Journal: Journal for ImmunoTherapy of Cancer (2023)

Immune checkpoint inhibitors (ICIs) have transformed the landscape of solid cancer management. These drugs carry a risk of novel side effects, which have become known as immune-related adverse events (irAEs). Traditionally, irAEs have been managed empirically with corticosteroids. A subset of these may be steroid refractory and as more evidence emerges about their distinct pathogeneses, a more tailored approach is required. Here, we report the use of a Janus kinase (JAK) inhibitor, baricitinib, in a patient with chronic inflammatory demyelinating polyneuropathy secondary to ICI use. We also review the current literature with regards to the use of these inhibitors in the management of irAEs. Modulation of the JAK pathway warrants further investigation in the targeted management of irAEs.
3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study
Authors: Hui Zhang, Chaolin Huang, Xiaoying Gu, Yeming Wang, Xia Li, Min Liu, Qiongya Wang, Jiuyang Xu, Yimin Wang, Huaping Dai, Dingyu Zhang, Bin Cao
Journal: The Lancet Respiratory Medicine (2023)
Seeding a planetary health education revolution: institutional sign-on challenge
Authors: Courtney Howard, Geneviève Moineau, Julien Poitras, Nicole Redvers, Jemilah Mahmood, Mohamed Eissa, Lujain Al Qodmani, Teddie Potter, Samantha Green, Carlos A Faerron Guzman
Journal: The Lancet (2023)
The effect of temporal data aggregation to assess the impact of changing temperatures in Europe: an epidemiological modelling study
Authors: Joan Ballester, Kim Robin van Daalen, Zhao-Yue Chen, Hicham Achebak, Josep M. Antó, Xavier Basagaña, Jean-Marie Robine, François R. Herrmann, Cathryn Tonne, Jan C. Semenza, Rachel Lowe
Journal: The Lancet Regional Health - Europe (2023)

Daily time-series regression models are commonly used to estimate the lagged nonlinear relation between temperature and mortality. A major impediment to this type of analysis is the restricted access to daily health records. The use of weekly and monthly data represents a possible solution unexplored to date.
A decade of Campylobacter and Campylobacter bacteraemias in a district general hospital and the surrounding London and South East region, England
Authors: Alice Graham, Lois Hawkins, Sooria Balasegaram, Subha Narasimhan, John Wain, John Clarke, Rohini Manuel
Journal: Journal of Infection (2023)

Campylobacter bacteraemia is a rare complication of the most common bacterial gastrointestinal infection but is associated with significant morbidity and mortality. There is limited data describing current trends in surveillance and antimicrobial resistance for the Campylobacter strains involved. At the Epsom and St Helier's University Hospital (ESTH), we noted a marked increase in Campylobacter bacteraemia infections in 2021.
Cancer screening in China: a steep road from evidence to implementation
Authors: Changfa Xia, Partha Basu, Barnett S Kramer, He Li, Chunfeng Qu, Xue Qin Yu, Karen Canfell, Youlin Qiao, Bruce K Armstrong, Wanqing Chen
Journal: The Lancet Public Health (2023)

Cancer screening has the potential to decrease mortality from several common cancer types. The first cancer screening programme in China was initiated in 1958 and the Cancer High Incidence Fields established in the 1970s have provided an extensive source of information for national cancer screening programmes. From 2012 onwards, four ongoing national cancer screening programmes have targeted eight cancer types: cervical, breast, colorectal, lung, oesophageal, stomach, liver, and nasopharyngeal cancers. By synthesising evidence from pilot screening programmes and population-based studies for various screening tests, China has developed a series of cancer screening guidelines. Nevertheless, challenges remain for the implementation of a fully successful population-based programme. The aim of this Review is to highlight the key milestones and the current status of cancer screening in China, describe what has been achieved to date, and identify the barriers in transitioning from evidence to implementation. We also make a set of implementation recommendations on the basis of the Chinese experience, which might be useful in the establishment of cancer screening programmes in other countries.
A tumor-associated heparan sulfate-related glycosaminoglycan promotes the generation of functional regulatory T cells
Authors: Leticia Martín-Cruz, Marcos Viñuela, Ioanna Kalograiaki, Alba Angelina, Paola Oquist-Phillips, Irene Real-Arévalo, Francisco Javier Cañada, José Ignacio Tudela, Luis Moltó, Jesús Moreno-Sierra, José Luis Subiza, Oscar Palomares
Journal: Cellular and Molecular Immunology (2023)

Abstract Functional Tregs play a key role in tumor development and progression, representing a major barrier to anticancer immunity. The mechanisms by which Tregs are generated in cancer and the influence of the tumor microenvironment on these processes remain incompletely understood. Herein, by using NMR, chemoenzymatic structural assays and a plethora of in vitro and in vivo functional analyses, we demonstrate that the tumoral carbohydrate A10 (Ca10), a cell-surface carbohydrate derived from Ehrlich’s tumor (ET) cells, is a heparan sulfate-related proteoglycan that enhances glycolysis and promotes the development of tolerogenic features in human DCs. Ca10-stimulated human DCs generate highly suppressive Tregs by mechanisms partially dependent on metabolic reprogramming, PD-L1, IL-10, and IDO. Ca10 also reprograms the differentiation of human monocytes into DCs with tolerogenic features. In solid ET-bearing mice, we found positive correlations between Ca10 serum levels, tumor size and splenic Treg numbers. Administration of isolated Ca10 also increases the proportion of splenic Tregs in tumor-free mice. Remarkably, we provide evidence supporting the presence of a circulating human Ca10 counterpart (Ca10H) and show, for the first time, that serum levels of Ca10H are increased in patients suffering from different cancer types compared to healthy individuals. Of note, these levels are higher in prostate cancer patients with bone metastases than in prostate cancer patients without metastases. Collectively, we reveal novel molecular mechanisms by which heparan sulfate-related structures associated with tumor cells promote the generation of functional Tregs in cancer. The discovery of this novel structural-functional relationship may open new avenues of research with important clinical implications in cancer treatment.
Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the ICF syndrome gene Zbtb24
Authors: Zhengzhou Ying, Swanand Hardikar, Joshua B. Plummer, Tewfik Hamidi, Bin Liu, Yueping Chen, Jianjun Shen, Yunxiang Mu, Kevin M. McBride, Taiping Chen
Journal: Cellular and Molecular Immunology (2023)
Magnet-assisted double-wire technique for patient with difficult endoscopic retrograde cholangiopancreatography cannulation
Authors: Hui Gong, Zhiyin Huang, LinJie Guo, Wenjuan Yang, Bing Hu
Journal: Endoscopy (2023)

A 70-year-old man was referred to our hospital with acute abdominal pain, jaundice, and fever. Magnetic resonance cholangiopancreatography showed a dilated common bile duct obstructed by an 11 × 7 mm fusiform gallstone. Total bilirubin was 38.96 µmol/L. After anti-infection and fluid rehydration, endoscopic retrograde cholangiopancreatography (ERCP) was performed.
A deathly silence: why has the number of people found decomposed in England and Wales been rising?
Authors: Lucinda Hiam, Theodore Estrin-Serlui, Danny Dorling, Martin McKee, Jon Minton
Journal: Journal of the Royal Society of Medicine (2023)

Objectives The number of deaths occurring in private homes in England and Wales had been rising for years, increasingly rapidly from 2020. Media stories and research linked decomposing bodies found in private homes with pandemic-related social isolation. We aim to explore whether these incidents are one-offs or part of a wider trend. Design Descriptive analysis of publicly available Office for National Statistics (ONS) data. Setting England and Wales. Participants All residents of England and Wales, 1979 to 2020. Main outcome measures Using data from the Office for National Statistics, we calculate European Age Standardised Rates for deaths coded as R98 (‘unattended death’) and R99 (‘other ill-defined and unknown causes of mortality’) in the 10th version of the International Classification of Diseases (ICD-10), and the corresponding codes in ICD-9, by sex and age group from 1979 (when ICD-9 began) to 2020. These are proxy markers for deaths where decomposition precludes attribution of a specific cause at postmortem. Results While mortality from all other causes decreased from 1979 to 2020, the opposite was seen for deaths from R98 and R99 (or ‘undefined deaths’), with men more affected than women. There was a sharp rise in these deaths in both sexes but in men particularly in the 1990s and 2000s, coinciding with a time when overall mortality was rapidly improving. Conclusions The increase in people found dead from unknown causes suggests wider societal breakdowns of both formal and informal social support networks. They are concerning and warrant urgent further investigation. We call on national and international authorities to consider measures that would make it possible to identify these deaths more easily in routine data.
Innovative management of intestinal obstruction with colonic transendoscopic enteral tubing
Authors: You Yu, Faming Zhang, Bota Cui
Journal: Endoscopy (2023)

Managing intestinal obstruction in patients with Crohn's disease (CD) is clinically challenging if emergency surgery is to be avoided [1]. Here, we present a case involving a patient with CD suffering from acute intestinal obstruction who was unresponsive to conservative treatments and successfully avoided emergency surgery through a novel technique for bowel decompression.
The “furrow sign” in confirming proper gastric extent and direction of the myotomy at the end of peroral endoscopic myotomy
Authors: Hugo Uchima, Raquel Muñoz-González, Anna Calm, Noemí Caballero, Jorge Espinos, Vicente Moreno de Vega, Ingrid Marin
Journal: Endoscopy (2023)

Peroral endoscopic myotomy (POEM), first performed by Inoue in 2008, stands as a primary treatment for achalasia [1]. Ensuring the appropriate length of the gastric myotomy is crucial, as a myotomy that is too short can lead to an inadequate response. Conversely, excessive length can result in a higher incidence of moderate reflux esophagitis without enhancing clinical effectiveness [2] [3]. While various landmarks and methods guide the proper extent of the tunnel [4] [5], a straightforward approach to confirm the end of the myotomy is lacking.
Single-session endoscopic ultrasound-directed transgastric endoscopy for treatment of upper gastrointestinal bleeding after Roux-en-Y gastric bypass
Authors: Jordan Burlen, Albert Manudhane, Luke Roberts, Anna Cecilia Amaral, Georgios I. Papachristou, Samuel Han
Journal: Endoscopy (2023)

Endoscopic ultrasound (EUS)-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP) – also known as EDGE – for the purpose of accessing the duodenum to perform EUS or ERCP has been well described in patients who have undergone Roux-en-Y gastric bypass (RYGB) [1]. Few reports, however, have described the use of EDGE to manage upper gastrointestinal bleeding in patients with RYGB anatomy [2].
Double-endoscope endoscopic submucosal dissection with snare traction and loop stabilization for adenoma involving appendiceal orifice
Authors: Hsin-Yu Chen, Chung-Ying Lee, Chao-Wen Hsu, Jen-Hao Yeh, Tsung-Hsien Chen, Kun-Feng Tsai, Chu-Kuang Chou
Journal: Endoscopy (2023)

Traction during colorectal endoscopic submucosal dissection (ESD) is essential for tackling difficult lesions. Although conventional clip–band-based methods are easy to use, they are difficult to adjust, require flaps, and offer limited traction forces. Using snare traction during double-endoscope ESD (DE-ESD) has proven to be effective in reducing procedure time and overcoming complex anatomical challenges [1] [2].
Initiatives to increase colonoscopy capacity – is there an impact on polyp detection? A UK National Endoscopy Database analysis
Authors: Matthew D. Rutter, Linda Sharp, Liya Lu, Jamie Catlow
Journal: Endoscopy (2023)

Abstract Background To address mismatch between routine endoscopy capacity and demand, centers often implement initiatives to increase capacity, such as weekend working or using locums/agency staff (insourcing). However, there are concerns that such initiatives may negatively impact quality. We investigated polyp detection for weekend vs. weekday and insourced vs. standard procedures using data from the UK National Endoscopy Database. Methods We conducted a national, retrospective, cross-sectional study of diagnostic colonoscopies performed during 01/01–04/04/2019. The primary outcome was mean number of polyps (MNP) and the secondary outcome was polyp detection rate (PDR). Multi-level mixed-effect regression, fitting endoscopist as a random effect, was used to examine associations between procedure day (weekend/weekday) and type (insourced/standard) and these outcomes, adjusting for patient age, sex, and indication. Results 92 879 colonoscopies (weekends: 19 977 [21.5 %]; insourced: 9909 [10.7 %]) were performed by 2496 endoscopists. For weekend colonoscopies, patients were less often male or undergoing screening-related procedures; for insourced colonoscopies, patients were younger and less often undergoing screening-related procedures (all P &lt; 0.05). Fully adjusted MNP was significantly lower for weekend vs. weekday (incidence rate ratio [IRR] 0.86 [95 %CI 0.83–0.89]) and for insourced vs. standard procedures (IRR 0.91 [95 %CI 0.87–0.95]). MNP was highest for weekday standard procedures and lowest for weekend insourced procedures; there was no interaction between procedure day and type. Similar associations were found for PDR. Conclusions Strategies to increase colonoscopy capacity may negatively impact polyp detection and should be monitored for quality. Reasons for this unwarranted variation require investigation.
Calcified fibrous tumor in the stomach: a rare case of gastric submucosal tumor treated with endoscopic submucosal excavation
Authors: Liansong Ye, Meiting Liang, Shuai Bai, Xinyue Zhou, Ou Chen, Bing Hu, Yi Mou
Journal: Endoscopy (2023)

A 39-year-old woman presented with a small submucosal tumor in the posterior wall of gastric lower body ([Fig. 1]). She reported nonspecific gastrointestinal symptoms such as recurrent epigastric pain and abdominal distension for 4 years. There was no significant medical history. Physical examination revealed no obvious abnormalities. Endoscopic ultrasonography showed the hypoechoic tumor with a clear boundary and an endoluminal growth pattern, which originated from the muscularis propria ([Fig. 2]). Enhanced computed tomography confirmed the tumor in the gastric body ([Fig. 3]).
Dual‐Functional Injectable Hydrogel for Osteoarthritis Treatments
Authors: Lei Lei, Rui Cong, Yifei Ni, Xin Cui, Xulei Wang, Hongmei Ren, Zun Wang, Mengyuan Liu, Jiasheng Tu, Lei Jiang
Journal: Advanced Healthcare Materials (2023)

Abstract Osteoarthritis (OA) is a prevalent, chronic degenerative disease that affects people worldwide. It is characterized by the destruction of cartilage and inflammatory reactions. High levels of reactive oxygen species (ROS) cause oxidative stress, which damages lipids, proteins, and DNA, leading to cell damage and death. Furthermore, ROS also induces the production of inflammatory cytokines and cell chemotaxis, further worsening the inflammatory response and damaging cartilage resulted in limited movement. Herein, this work reports a dual‐functional injectable hydrogel, which can help inhibit inflammation by scavenging ROS and provide lubrication to reduce wear and tear on the joints. To create the hydrogel, 3‐aminophenylboronic acid modified hyaluronic acid is synthesized, then which is crosslinked with hydroxyl‐containing polyvinyl alcohol (PVA) to construct a dual dynamic covalent crosslinked hydrogel oHA‐PBA‐PVA gel, Gel (HPP). The hydrogel mentioned here possesses a unique bond structure that allows it to be injected, self‐heal, and provide lubrication. This innovative approach offers a new possibility for treating osteoarthritis by combining anti‐inflammatory and lubrication effects.
Cellular Architects at Work: Cells Building their Own Microgel Houses
Authors: Selin Bulut, Daniel Günther, Michelle Bund, Christina Haats, Thomas Bissing, Céline Bastard, Matthias Wessling, Laura De Laporte, Andrij Pich
Journal: Advanced Healthcare Materials (2023)

Microporous annealed particle (MAP) scaffolds are investigated for their application as injectable 3D constructs in the field of regenerative medicine and tissue repair. While available MAP scaffolds provide a stable interlinked matrix of microgels for cell culture, the infiltration depth and space for cells to grow inside the scaffolds is pre-determined by the void fraction during the assembly. In the case of MAP scaffolds fabricated from interlinked spherical microgels, a cellularity gradient can be observed with the highest cell density on the scaffold surface. Additionally, the interlinked microgel network limits the ability of cells to remodel their environment, which contradicts native tissue dynamics. In this work, a cell-induced interlinking method for MAP scaffold formation is established, which avoids the necessity of chemical crosslinkers and pre-engineered pores to achieve micro- or macropores in these 3D frameworks. This method enables cells to self-organize with microgels into dynamic tissue constructs, which can be further controlled by altering the microgel properties, the cell/microgel ratio, and well shape. To form a cell-induced interlinked scaffold, the cells are mixed with dextran-based microgels and function as a glue between the microgels, resulting in a more homogenous cell distribution throughout the scaffold with efficient cell-cell interactions.
CD8<sup>+</sup>chimeric antigen receptor T cells manufactured in absence of CD4<sup>+</sup>cells exhibit hypofunctional phenotype
Authors: Sang Yun Lee, Dong Hoon Lee, Wei Sun, Francisco Cervantes-Contreras, Ryan S Basom, Feinan Wu, Si Liu, Richa Rai, Hamid R Mirzaei, Shyril O’Steen, Damian J Green, Mazyar Shadman, Brian G Till
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Cell culture conditions during manufacturing can impact the clinical efficacy of chimeric antigen receptor (CAR) T cell products. Production methods have not been standardized because the optimal approach remains unknown. Separate CD4 + and CD8 + cultures offer a potential advantage but complicate manufacturing and may affect cell expansion and function. In a phase 1/2 clinical trial, we observed poor expansion of separate CD8 + cell cultures and hypothesized that coculture of CD4 + cells and CD8 + cells at a defined ratio at culture initiation would enhance CD8 + cell expansion and simplify manufacturing. Methods We generated CAR T cells either as separate CD4 + and CD8 + cells, or as combined cultures mixed in defined CD4:CD8 ratios at culture initiation. We assessed CAR T cell expansion, phenotype, function, gene expression, and in vivo activity of CAR T cells and compared these between separately expanded or mixed CAR T cell cultures. Results We found that the coculture of CD8 + CAR T cells with CD4 + cells markedly improves CD8 + cell expansion, and further discovered that CD8 + cells cultured in isolation exhibit a hypofunctional phenotype and transcriptional signature compared with those in mixed cultures with CD4 + cells. Cocultured CAR T cells also confer superior antitumor activity in vivo compared with separately expanded cells. The positive impact of CD4 + cells on CD8 + cells was mediated through both cytokines and direct cell contact, including CD40L-CD40 and CD70-CD27 interactions. Conclusions Our data indicate that CD4 + cell help during cell culture maintains robust CD8 + CAR T cell function, with implications for clinical cell manufacturing.